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临床试验/NCT05471583
NCT05471583Unknown不适用

Assessment of Endothelial Glycocalyx Dysfunction and Impaired Microcirculatory Perfusion During Cardiac Surgery to Improve Prediction of Post-operative Acute Kidney

King's College London1 个研究点 分布在 1 个国家目标入组 70 人开始时间: 2021年11月16日最近更新:
适应症

试验速览

阶段
不适用
入组人数
70
试验地点
1
主要终点
Acute kidney injury

研究概览

简要总结

Abstract Significance: Cardiac surgery-associated acute kidney injury (CSA-AKI) is common and has serious immediate and long-term sequelae. Better early prediction of those at highest risk and greater understanding of underlying pathological processes are needed to prevent or minimise damage.

Hypotheses

  • Dynamic changes in systemic endothelial glycocalyx (Glx) and microcirculatory parameters during coronary artery bypass graft (CABG) surgery are predictive of CSA-AKI.
  • Mechanisms for Glx degradation during CABG surgery are akin to those during sepsis Aims
  • Investigate Glx and microcirculatory health throughout CABG surgery and recovery and their association with CSA-AKI.
  • Explore association between inflammation and Glx degradation during CABG surgery.

Methodology

  1. Prospective cohort study: serial sampling and microcirculatory perfusion imaging of 70 patients undergoing CABG surgery with evaluation of CSA-AKI predictors, including plasma Syndecan-1.
  2. Examination of inflammation and cardiometabolic proteome and association with vascular changes
  3. In vitro mechanistic assessment of Glx degradation and relative timing of organelle exocytosis in cultured endothelial cells in response to patient serum, targeting identified candidate mediators.

Impact: Enhancing CSA-AKI risk stratification with new mechanistic biomarkers will enable individualised management of at-risk patients, and pathophysiological insights will create possible therapeutic targets, thus reducing morbidity, mortality and cost of CSA-AKI.

详细描述

Study design: Prospective cohort study.

The investigators will recruit 70 elective patients undergoing CABG surgery with and without cardiopulmonary bypass (CPB), with blood and urine sampling and assessment of microcirculatory perfusion by IDF in pre- peri- and post-operative periods, with informed written consent. The investigators have completed a feasibility study with successful recruitment and data collection at all time points and the current protocol and patient material have been reviewed by a patient representative.

Blood and urine samples will be analysed to consider markers of endothelial glycocalyx degradation (including syndecan-1 (SDC1)), endothelial activation (including thrombomodulin (TM)), and markers of renal tubular stress (NephroCheck).

Sublingual microcirculatory perfusion assessed by IDF imaging is painless and low risk and participant acceptability has been confirmed during the feasibility study. The process involves using a small handheld probe to gently press on the underside of the tongue and takes 3-10 minutes. Four video clips of 10s will be taken from each participant from different sites within the sublingual area. Videos will be exported as pseudonymised files for analysis. Image collection and analysis will be performed in accordance with international consensus recommendations, using a CytoCam video-microscope (Braedius Medical B.V., Huizen, The Netherlands). Images will be analysed using a dedicated software tool (Automated Vascular Analysis V.3.02, Microvision Medical, The Netherlands). Data generated will include flow and density-based measures of the microcirculation, including Perfused Vessel Density (PVD) and Microcirculatory Flow Index (MFI).

Peri-operative sampling and imaging will occur at predefined surgical time-points, in keeping with previous studies and informed by the feasibility study. Time-points were selected in anticipation of the most informative results, including point of peak "reperfusion" after final surgical anastomosis, and to minimise participant inconvenience (existing arterial line and urinary catheter tubing will be used) and to avoid surgical disruption and delays (IDF is quicker during anaesthesia and previous studies have shown negligible change between baseline and assessment immediately after anaesthesia prior to surgery).

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Listed for CABG surgery with or without CPB, age >18 years, able and willing to give written informed consent.

排除标准

  • Unable / unwilling to provide blood samples or undergo IDF imaging, cross-clamp fibrillation technique, already on renal replacement therapy

结局指标

主要结局

Acute kidney injury

时间窗: 7 days

as per Kidney Disease Improving Global Outcomes (KDIGO) guidelines

次要结局

  • NephroCheck(1 hour post-op)
  • microvascular flow index(up to 1 hour post-op)
  • thrombomodulin change(through study completion: 24 hours)
  • Syndecan-1 change(through study completion: 24 hours)
  • perfused vessel density(up to 1 hour post-op)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Dr Jennifer Joslin

Clinical Research Fellow

King's College London

研究点 (1)

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